Properties of GABAergic Neurons Containing Calcium-Permeable Kainate and AMPA-Receptors

Зинченко, В. П.; Kosenkov, Artem M.; Gaidin, Sergei G.; Сергеев, А. И.; Долгачева, Л. П.; Tuleukhanov, Sultan

doi:10.3390/life11121309

Cited by 6 publications

(7 citation statements)

References 59 publications

(105 reference statements)

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“…We have previously reported the methods of vital identification of neurons expressing calcium-permeable AMPA and KA receptors (CP-AMPARs and CP-KARs) using Ca 2+ imaging ( Zinchenko et al, 2021 ; Gaidin et al, 2023 ). In order to visualize neurons expressing CP-AMPARs and CP-KARs in hippocampal neuron-glial cultures, we recorded changes in the cytosolic Ca 2+ concentration ([Ca 2+ ] i ) induced by agonists and antagonists of these receptors.…”

Section: Resultsmentioning

confidence: 99%

“…In order to visualize neurons expressing CP-AMPARs and CP-KARs in hippocampal neuron-glial cultures, we recorded changes in the cytosolic Ca 2+ concentration ([Ca 2+ ] i ) induced by agonists and antagonists of these receptors. The domoic acid (DoA) was used as an agonist of both receptors ( Hogberg and Bal-Price, 2011 ; Zinchenko et al, 2021 ). ATPA was used as a selective agonist of GluK1-containing CP-KARs ( Maiorov et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…The CP-AMPA receptor antagonist NASPM reverses this effect. NASPM causes activation of interneurons and inhibition of glutamatergic neurons ( Zinchenko et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that in the hippocampus of adult rats, CP-AMPARs are expressed mainly in GABAergic neurons, and these neurons account for about 35% of all GABAergic neurons (Zinchenko et al, 2020). Moreover GABAergic neurons expressing CP-AMPARs can innervate other GABAergic interneurons expressing CP-KARs and thus disinhibit glutamatergic neurons during epileptiform activity (Zinchenko et al, 2020(Zinchenko et al, , 2021. The CP-AMPA receptor antagonist NASPM reverses this effect.…”

Section: Introductionmentioning

confidence: 99%

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Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Zinchenko,

Teplov,

Kosenkov

et al. 2024

Front. Synaptic Neurosci.

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IntroductionEpileptiform activity is the most striking result of hyperexcitation of a group of neurons that can occur in different brain regions and then spread to other sites. Later it was shown that these rhythms have a cellular correlate in vitro called paroxysmal depolarization shift (PDS). In 13–15 DIV neuron-glial cell culture, inhibition of the GABA(A) receptors induces bursts of action potential in the form of clasters PDS and oscillations of intracellular Ca2+ concentration ([Ca2+]i). We demonstrate that GABAergic neurons expressing calcium-permeable AMPA receptors (CP-AMPARs) as well as Kv7-type potassium channels regulate hippocampal glutamatergic neurons’ excitability during epileptiform activity in culture.MethodsA combination of whole-cell patch-clamp in current clamp mode and calcium imaging microscopy was used to simultaneously register membrane potential and [Ca2+]i level. To identify GABAergic cell cultures were fixed and stained with antibodies against glutamate decarboxylase GAD 65/67 and neuron-specific enolase (NSE) after vital [Ca2+]i imaging.Results and discussionIt was shown that CP-AMPARs are involved in the regulation of the PDS clusters and [Ca2+]i pulses accompanied them. Activation of CP-AMPARs of GABAergic neurons is thought to cause the release of GABA, which activates the GABA(B) receptors of other GABAergic interneurons. It is assumed that activation of these GABA(B) receptors leads to the release of beta-gamma subunits of Gi protein, which activate potassium channels, resulting in hyperpolarization and inhibition of these interneurons. The latter causes disinhibition of glutamatergic neurons, the targets of these interneurons. In turn, the CP-AMPAR antagonist, NASPM, has the opposite effect. Measurement of membrane potential in GABAergic neurons by the patch-clamp method in whole-cell configuration demonstrated that NASPM suppresses hyperpolarization in clusters and individual PDSs. It is believed that Kv7-type potassium channels are involved in the control of hyperpolarization during epileptiform activity. The blocker of Kv7 channels, XE 991, mimicked the effect of the CP-AMPARs antagonist on PDS clusters. Both drugs increased the duration of the PDS cluster. In turn, the Kv7 activator, retigabine, decreased the duration of the PDS cluster and Ca2+ pulse. In addition, retigabine led to deep posthyperpolarization at the end of the PDS cluster. The Kv7 channel is believed to be involved in the formation of PDS, as the channel blocker reduced the rate of hyperpolarization in the PDS almost three times. Thus, GABAergic neurons expressing CP-AMPARs, regulate the membrane potential of innervated glutamatergic neurons by modulating the activity of postsynaptic potassium channels of other GABAergic neurons.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…The CP-AMPA receptor antagonist NASPM reverses this effect. NASPM causes activation of interneurons and inhibition of glutamatergic neurons ( Zinchenko et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Zinchenko,

Teplov,

Kosenkov

et al. 2024

Front. Synaptic Neurosci.

Self Cite

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show abstract

“…It deserves mention that the present work has been focussed on neurotransmission at CA3/CA1 synapses, which prevents uncritical generalization of our results to brain pathways different from CA3/CA1. Furthermore, the neurochemical assays were performed in the whole hippocampus, which does not rule out the possibility that the increase in expression of GluA2, and in particular of unedited GluA2, is localized in hippocampal inhibitory GABA neurons, where CP-AMPA receptors are physiologically expressed (Albuquerque et al, 1999;Zinchenko et al, 2021). Similarly, we did not investigate a possible dorsoventral distribution of GluA2 overexpression and the electrophysiological analysis were limited to dorsal hippocampus.…”

Section: Discussionmentioning

confidence: 99%